Despite its high prevalence, generalized anxiety disorder (GAD) has been relatively under studied compared with other anxiety disorders. Patients with GAD worry excessively about an uncertain future that they believe will be aversive. Despite evidence that worry concerns the future, most experimental paradigms studying GAD focus only on direct responses to evocative material. With the advent of increasingly sophisticated assessments of neural responsivity, it is now essential to probe the anticipatory nature of GAD alongside responses to affective stimuli. Another important factor in this form of psychopathology is the chronic nature of anxiety and difficulty controlling negative thoughts once they are initiated. Difficulty controlling worry is one of the diagnostic criteria for GAD well supported by self-report data in these patients. To provide evidence for the neurobiological substrate of chronic, difficult to control aversive experiences in GAD, the measurement of physiological responses in the aftermath of aversive stimulus presentations (recovery) is warranted. The work planned will focus on the neural signature of processing negative emotional information in GAD using functional magnetic resonance brain imaging (fMRI). The paradigm will take an innovative approach in examining emotional reactivity including anticipation of, response to, and recovery from aversive visual stimuli in a single study. Comparisons will be made between GAD and control subjects with no current or past psychiatric disorder. Contrasts will also be made between GAD patients and major depressive disorder (MDD) patients as well as patients with both conditions. GAD patients are expected to show greater amygdala activity as well as activity in the insula and several key areas implicated in the anticipation of aversion during anticipation of emotional stimuli than non-anxious controls. In response to aversive stimuli, GAD patients are expected to show less reactivity in these regions than non-anxious controls. For recovery, GAD patients are expected to be similar to MDD patients in showing sustained neural responding in the targeted brain regions following aversive stimuli. PUBLIC HEALTH RELEVANCE: By better understanding the processes of anticipation, response, and recovery in anxious and depressive populations, new strategies for treatment may benefit individuals and reduce the societal burden of their symptoms. These data will allow clinicians to know which stage of emotional processing for a particular group of patients might most benefit from interventions targeting that stage. These data may also suggest sensitive precursors of affective disorders in individuals with genetic susceptibility to anxious and depressive traits with the goal to ultimately prevent the clinical syndrome from developing in these individuals.